Assessing the risk of intentional self-harm in montelukast users: an updated Sentinel System analysis using ICD-10 coding

Abstract

Background

Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS).

Methods

Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps.

Results

Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses.

Conclusion

Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9.

Keywords:

• Suicide
• leukotriene receptor antagonist
• neuropsychiatric events
• inhaled corticosteroids
• ICD-9 codes

Acknowledgements

Thanks to the following: Data Partners who provided data used in the analysis: CVS Health, Blue Bell, PA; Carelon Research/Elevance Health, Wilmington, DE; Duke University School of Medicine, Department of Population Health Sciences, Durham, NC, through the Centers for Medicare and Medicaid Services which provided data; Humana Healthcare Research Inc., Louisville, KY; OptumInsight Life Sciences Inc., Boston, MA

Disclaimer

The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government

Disclosure statement

The authors declare that they have no relevant conflicts of interest.

Declaration of interest

No potential conflict of interest was reported by the author(s).

Ethical approval

The FDA approved the study protocol including statistical analysis plan, and reviewed and approved this manuscript. Coauthors from the FDA participated in the results interpretation and in the preparation and decision to submit the manuscript for publication. The FDA had no role in data collection, management, or analysis.

Additional information

Funding

This project was supported by Task Order 75F40122F19005 under Master Agreement 75F40119D10037 from the US Food and Drug Administration (FDA). This project was supported in part by an appointment to the ORISE Research Participation Program at the Center for Drug Evaluation and Research (CDER) administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and Food and Drug Administration Center for Drug Evaluation and Research (CDER).